Residual risk of transfusion-associated infectious disease persists despite improved donor testing. Donor testing cannot protect prospectively against new viruses which may enter the population, such as HIV in 1979.Solvent- detergent treatment, introduced for plasma and plasma-fractions, is only effective against enveloped viruses (env-V). The overall program objective is to develop effective and practical decontamination processes for non-cellular transfusion products, including recombinant biologicals, which are effective against env-V and non-enveloped viruses (non-env-V), such as hepatitis A virus (HAV) and parvovirus B19 (PVB19). The goal of this application is to develop psoralen (Ps)-mediated photochemical decontamination (PCD) methods effective against at least 10(6)/ml non-env-V and env-V in non-cellular therapeutic biologicals. This goal will be achieved through the following specific aims: 1) to develop methods using a novel Ps derivative (S-59) plus ultraviolet light (UVA/UBV) to inactivate significant viral non-env-V and env-V pathogens; 2) to test further novel Ps that enhance nucleic acid inactivation specificity and efficacy for non-env-V while reducing mutagenicity using structure function matrices developed for Ps derivatives based on inactivation of env-V pathogens as the primary determinant of function; 3) to develop an ultrasonic flow system to facilitate Ps mediated inactivation on non- env-V.Efficacy will be evaluated using HAV and poliovirus, both characterized by impenetrable outer capsid structures; and 4) to utilize microwave radiation (MR) and temperature to enhance Ps-UVA viral inactivation. Efficacy will be evaluated initially using bacteriophage X 174 as a model non-decontaminate recombinant human proteins, e.g., Factor VIII. Inactivation of non-env-V and env-V pathogens will be studied using high-intensity UVA in a flow system under reduced ambient 02. The effects on protein yield, function, structure, and neo- antigenicity will be evaluated using coagulation assays, radiolabel incorporation, mass spectroscopy, and an immune tolerance assay.